Abstract
Global gene expression data combined with bioinformatic analysis provides strong evidence that mammalian miRNAs mediate repression of gene expression primarily through binding sites within the 3′ untranslated region (UTR). Using RNA induced silencing complex immunoprecipitation (RISC-IP) techniques we have identified multiple cellular targets for a human cytomegalovirus (HCMV) miRNA, miR-US25-1. Strikingly, this miRNA binds target sites primarily within 5′UTRs, mediating significant reduction in gene expression. Intriguingly, many of the genes targeted by miR-US25-1 are associated with cell cycle control, including cyclin E2, BRCC3, EID1, MAPRE2, and CD147, suggesting that miR-US25-1 is targeting genes within a related pathway. Deletion of miR-US25-1 from HCMV results in over expression of cyclin E2 in the context of viral infection. Our studies demonstrate that a viral miRNA mediates translational repression of multiple cellular genes by targeting mRNA 5′UTRs.
Highlights
The recent discovery of a new class of regulatory genes known as microRNAs has resulted in a paradigm shift in gene regulation research. miRNAs are small single-stranded RNA species of approximately 20–24 bases in length that regulate gene expression through post transcriptional mechanisms [1]
Our studies demonstrate that a viral miRNA mediates translational repression of multiple cellular genes by targeting mRNA 59UTRs
Regulation of gene expression is as important as the genes themselves in determining the diverse array of living creatures we see in nature
Summary
The recent discovery of a new class of regulatory genes known as microRNAs (miRNAs) has resulted in a paradigm shift in gene regulation research. miRNAs are small single-stranded RNA species of approximately 20–24 bases in length that regulate gene expression through post transcriptional mechanisms [1]. Expression of miRNAs is thought to be ubiquitous among multicellular eukaryotes [2]. Targets for the majority of viral miRNAs are currently unknown due to the difficulty involved in identifying novel target transcripts. This remains one of the major challenges in elucidating the function of miRNAs. recent reports have begun to elucidate the various roles of viral miRNAs. recent reports have begun to elucidate the various roles of viral miRNAs These include blocking apoptosis, immune evasion and regulation of viral replication through targeting of both cellular and viral gene expression [4,5]
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